Transport of 5-fluorouracil and uracil into human erythrocytes

• Published in: Biochemical pharmacology Vol. 46; no. 3; pp. 503 - 510
• Main Authors: Domin, Barbara A., Mahony, William B., Zimmerman, Thomas P.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 03.08.1993; Elsevier Science
• Subjects: Adenine - metabolism; Antineoplastic agents; Biological and medical sciences; Biological Transport; Chemotherapy; Erythrocytes - metabolism; Fluorouracil - metabolism; Humans; Hypoxanthine; Hypoxanthines - metabolism; Kinetics; Medical sciences; Nucleic Acids - metabolism; Nucleosides - metabolism; Papaverine; Pharmacology. Drug treatments; Tritium; Uracil - metabolism; NBMPR; Gua; Ade; Ura; Hepes; Hyp; 5-FU; Antineoplastic agent; Human; Biological transport; Red blood cell; In vitro; Pyrimidine nucleotide; Uracil; Uptake; Mechanism
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/0006-2952(93)90527-4

The transport of 5-fluorouracil (5-FU) and uracil into human erythrocytes has been investigated under initial velocity conditions with an “inhibitor-stop” assay using a cold papaverine solution to terminate influx. At 37° and pH 7.3, 5-FU influx was nonconcentrative; was partially inhibited by adenine, hypoxanthine, thymine, and uracil; and was insensitive to inhibition by nucleosides or inhibitors of nucleoside transport. Inhibition of the influx of 5-FU or uracil by adenine (3.0 mM) did not increase when other pyrimidines or inhibitors of nucleoside transport were combined with adenine. 5-FU and uracil exhibited similar saturable ( K m 4 mM, V max 500 pmol/sec/5 μL cells) and nonsaturable (rate constant 80 pmol/sec/mM/5 μL cells) components of influx. 5-FU, uracil, adenine, and hypoxanthine were competitive inhibitors of each other's influx with K i , values matching their respective K m values for influx. We conclude that 5-FU and uracil enter human erythrocytes at similar rates via both nonfacilitated diffusion and the same carrier that transports adenine and hypoxanthine.